Cited 2 times in
A phase 1 dose-escalation and dose-expansion study to assess the safety and efficacy of CKD-516, a novel vascular disrupting agent, in combination with Irinotecan in patients with previously treated metastatic colorectal cancer
DC Field | Value | Language |
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dc.contributor.author | 신상준 | - |
dc.contributor.author | 안중배 | - |
dc.date.accessioned | 2022-11-24T00:32:03Z | - |
dc.date.available | 2022-11-24T00:32:03Z | - |
dc.date.issued | 2021-10 | - |
dc.identifier.issn | 0167-6997 | - |
dc.identifier.uri | https://ir.ymlib.yonsei.ac.kr/handle/22282913/190746 | - |
dc.description.abstract | Introduction The combination of an anti-angiogenic agent with cytotoxic chemotherapy is a standard treatment strategy for metastatic colorectal cancer. CKD-516 is an oral vascular disrupting agent that was preliminarily shown to be safe and efficacious as a monotherapy in refractory solid cancers. We evaluated the recommended phase 2 dose, safety, and preliminary efficacy of CKD-516 in combination with irinotecan in treatment-refractory metastatic colorectal cancer. Methods This phase 1 dose-escalation and dose-expansion study included patients with treatment-refractory metastatic colorectal cancer. CKD-516 tablets were administered for five consecutive days followed by two days off in combination with intravenous irinotecan (120 mg/m2) administered on day one of each treatment cycle every two weeks. A traditional 3 + 3 dose-escalation design was used. Results In total, 16 and 23 patients were enrolled in the dose-escalation and dose-expansion cohorts, respectively. The most common adverse events included diarrhea (79%), nausea (74%), vomiting (67%), and neutropenia (62%). No dose-limiting toxicity occurred, and the recommended phase 2 dose was determined at CKD-516/irinotecan doses of 11/120 mg/m2. No cases of cardiac ischemia, cardiac dysfunction, or thromboembolism were reported. Among the 34 patients with available tumor response assessments, one patient achieved partial response (3%) and 26 patients achieved stable disease (76%). The median progression-free survival and overall survival were 4.1 and 11.6 months, respectively. Conclusion This phase 1 study showed that the combination of oral CKD-516 and irinotecan is safe and tolerable in metastatic, treatment-refractory colorectal patients and showed favorable efficacy outcomes. Further studies to confirm these preliminary findings are warranted. Trial registration number NCT03076957 (Registered at March 10, 2017). | - |
dc.description.statementOfResponsibility | restriction | - |
dc.language | English | - |
dc.publisher | Springer | - |
dc.relation.isPartOf | INVESTIGATIONAL NEW DRUGS | - |
dc.rights | CC BY-NC-ND 2.0 KR | - |
dc.subject.MESH | Adult | - |
dc.subject.MESH | Aged | - |
dc.subject.MESH | Antineoplastic Agents / administration & dosage | - |
dc.subject.MESH | Antineoplastic Agents / adverse effects | - |
dc.subject.MESH | Antineoplastic Agents / pharmacokinetics | - |
dc.subject.MESH | Antineoplastic Agents / therapeutic use* | - |
dc.subject.MESH | Antineoplastic Combined Chemotherapy Protocols / therapeutic use | - |
dc.subject.MESH | Area Under Curve | - |
dc.subject.MESH | Benzophenones / administration & dosage | - |
dc.subject.MESH | Benzophenones / adverse effects | - |
dc.subject.MESH | Benzophenones / pharmacokinetics | - |
dc.subject.MESH | Benzophenones / therapeutic use* | - |
dc.subject.MESH | Colorectal Neoplasms / drug therapy* | - |
dc.subject.MESH | Colorectal Neoplasms / pathology | - |
dc.subject.MESH | Dose-Response Relationship, Drug | - |
dc.subject.MESH | Female | - |
dc.subject.MESH | Half-Life | - |
dc.subject.MESH | Humans | - |
dc.subject.MESH | Irinotecan / therapeutic use | - |
dc.subject.MESH | Kaplan-Meier Estimate | - |
dc.subject.MESH | Male | - |
dc.subject.MESH | Maximum Tolerated Dose | - |
dc.subject.MESH | Metabolic Clearance Rate | - |
dc.subject.MESH | Middle Aged | - |
dc.subject.MESH | Neoplasm Metastasis | - |
dc.subject.MESH | Progression-Free Survival | - |
dc.subject.MESH | Valine / administration & dosage | - |
dc.subject.MESH | Valine / adverse effects | - |
dc.subject.MESH | Valine / analogs & derivatives* | - |
dc.subject.MESH | Valine / pharmacokinetics | - |
dc.subject.MESH | Valine / therapeutic use | - |
dc.title | A phase 1 dose-escalation and dose-expansion study to assess the safety and efficacy of CKD-516, a novel vascular disrupting agent, in combination with Irinotecan in patients with previously treated metastatic colorectal cancer | - |
dc.type | Article | - |
dc.contributor.college | College of Medicine (의과대학) | - |
dc.contributor.department | Dept. of Internal Medicine (내과학교실) | - |
dc.contributor.googleauthor | Hyehyun Jeong | - |
dc.contributor.googleauthor | Yong Sang Hong | - |
dc.contributor.googleauthor | Jeong Eun Kim | - |
dc.contributor.googleauthor | Hyeong-Seok Lim | - |
dc.contributor.googleauthor | Joong Bae Ahn | - |
dc.contributor.googleauthor | Sang Joon Shin | - |
dc.contributor.googleauthor | Young Suk Park | - |
dc.contributor.googleauthor | Seung Tae Kim | - |
dc.contributor.googleauthor | Sae-Won Han | - |
dc.contributor.googleauthor | Tae-You Kim | - |
dc.contributor.googleauthor | Tae Won Kim | - |
dc.identifier.doi | 10.1007/s10637-021-01110-9 | - |
dc.contributor.localId | A02105 | - |
dc.contributor.localId | A02262 | - |
dc.relation.journalcode | J01184 | - |
dc.identifier.eissn | 1573-0646 | - |
dc.identifier.pmid | 33829355 | - |
dc.identifier.url | https://link.springer.com/article/10.1007/s10637-021-01110-9 | - |
dc.subject.keyword | CKD-516 | - |
dc.subject.keyword | Colorectal cancer | - |
dc.subject.keyword | Irinotecan | - |
dc.subject.keyword | Vascular-disrupting agent | - |
dc.contributor.alternativeName | Shin, Sang Joon | - |
dc.contributor.affiliatedAuthor | 신상준 | - |
dc.contributor.affiliatedAuthor | 안중배 | - |
dc.citation.volume | 39 | - |
dc.citation.number | 5 | - |
dc.citation.startPage | 1335 | - |
dc.citation.endPage | 1347 | - |
dc.identifier.bibliographicCitation | INVESTIGATIONAL NEW DRUGS, Vol.39(5) : 1335-1347, 2021-10 | - |
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